Refine
Year of publication
Document Type
- Article (52)
- Postprint (13)
- Review (2)
- Monograph/Edited Volume (1)
Language
- English (68)
Is part of the Bibliography
- yes (68)
Keywords
- Quantitative Trait Locus (4)
- Quantitative Trait Locus analysis (4)
- metabolomics (4)
- recombinant inbred line (4)
- Gene Ontology (2)
- Glioma (2)
- Partial Little Square (2)
- Phosphorylation Site (2)
- dominance effect (2)
- feature selection (2)
- gene expression (2)
- heterosis (2)
- phosphorylated amino acid (2)
- prediction (2)
- recombinant inbred line population (2)
- single nucleotide polymorphism mapping (2)
- slim term (2)
- Algebraic geometry (1)
- Arabidopsis thaliana (1)
- Bifurcation parameters (1)
- Biomass (1)
- Calvin cycle (1)
- Complexity (1)
- Conjunctive Normal Form (1)
- Constraint-based approaches (1)
- Correlation networks (1)
- DNA methylation (1)
- Data integration (1)
- Dickkopf 1 (1)
- Disjunctive Normal Form (1)
- Docking interactions (1)
- Evolution (1)
- External structural measures (1)
- Full Adder (1)
- Fusion (1)
- Gap junction (1)
- Gene function prediction (1)
- Gene regulatory network (1)
- Gene structure (1)
- Genotype Inference (1)
- Gliomas (1)
- Graph theory (1)
- HOMA (1)
- Haplotype Inference (1)
- Human mesenchymal stem cells (1)
- Hybrid prediction (1)
- Hypoxia (1)
- Intercellular crosstalk (1)
- LASSO (1)
- Maize (1)
- Mesenchymal stem cell (1)
- Metabolic networks (1)
- Metabolite profiles (1)
- Microarray data (1)
- Multistationarity (1)
- Mutual Information (1)
- NP-completeness (1)
- Phenomics (1)
- Regression (1)
- Robustness (1)
- STAT6 (1)
- Sequence alignment (1)
- Signal-transduction (1)
- Small-world networks (1)
- Support vector machines (1)
- Syncytium (1)
- Th2 cells (1)
- Transcription factors (1)
- Transductive learning (1)
- U87 glioma cells (1)
- Zea mays (1)
- action language (1)
- algorithms (1)
- answer set programming (1)
- arabidopsis (1)
- balance analysis (1)
- biochemical networks (1)
- biological network model (1)
- biological robustness (1)
- biomarker (1)
- biomass (1)
- centrality (1)
- combinatorics (1)
- comparative proteomics (1)
- computational biochemistry (1)
- computational molecular biology (1)
- couple reaction (1)
- coupling relationship (1)
- databases (1)
- decision tree (1)
- differential gene expression (1)
- efficient (1)
- endothelial progenitor cell (1)
- fasting glucose (1)
- functional genomics (1)
- gene expression matrix (1)
- gene-expression (1)
- genetic variability (1)
- hematopoietic stem cell (1)
- heterogeneous tissue (1)
- homogeneous cell population (1)
- impaired glucose tolerance (1)
- information (1)
- insulin (1)
- insulin resistance (1)
- kidney cancer (1)
- linear programming problem (1)
- linkage disequilibrium (1)
- lipoxygenase (1)
- mass accuracy (1)
- metabolic network (1)
- metabolic networks (1)
- metabolic regulation (1)
- metabolism (1)
- metabolite (1)
- metabolite profiling (1)
- metastasis (1)
- microarray data (1)
- microdissection (1)
- models (1)
- morphological analysis (1)
- muscle development (1)
- null model (1)
- package (1)
- pathways (1)
- phenotype (1)
- plant biology (1)
- plasma (1)
- polycystic ovary syndrome (1)
- potato (1)
- potato tuber (1)
- principal component (1)
- proinsulin (1)
- protease inhibitor (1)
- protein isoforms (1)
- pure parsimony (1)
- quantile normalization (1)
- random forest (1)
- randomization (1)
- reconstruction (1)
- regression (1)
- regular exercise training (1)
- resistance (1)
- reversible reaction (1)
- saccharomyces-cerevisiae (1)
- seedlings (1)
- selection (1)
- significance (1)
- solanum (1)
- stress-response (1)
- subcellular localization (1)
- support vector machine (1)
- systems biology (1)
- transcript profiling (1)
- trehalose synthesis (1)
- type 2 diabetes (1)
- type 2 diabetes mellitus (1)
Background: Biological systems adapt to changing environments by reorganizing their cellula r and physiological program with metabolites representing one important response level. Different stresses lead to both conserved and specific responses on the metabolite level which should be reflected in the underl ying metabolic network. Methodology/Principal Findings: Starting from experimental data obtained by a GC-MS based high-throughput metabolic profiling technology we here develop an approach that: (1) extracts network representations from metabolic conditiondependent data by using pairwise correlations, (2) determines the sets of stable and condition-dependent correlations based on a combination of statistical significance and homogeneity tests, and (3) can identify metabolites related to the stress response, which goes beyond simple ob servation s about the changes of metabolic concentrations. The approach was tested with Escherichia colias a model organism observed under four different environmental stress conditions (cold stress, heat stress, oxidative stress, lactose diau xie) and control unperturbed conditions. By constructing the stable network component, which displays a scale free topology and small-world characteristics, we demonstrated that: (1) metabolite hubs in this reconstructed correlation networks are significantly enriched for those contained in biochemical networks such as EcoCyc, (2) particular components of the stable network are enriched for functionally related biochemical path ways, and (3) ind ependently of the response scale, based on their importance in the reorganization of the cor relation network a set of metabolites can be identified which represent hypothetical candidates for adjusting to a stress-specific response. Conclusions/Significance: Network-based tools allowed the identification of stress-dependent and general metabolic correlation networks. This correlation-network-ba sed approach does not rely on major changes in concentration to identify metabolites important for st ress adaptation, but rather on the changes in network properties with respect to metabolites. This should represent a useful complementary technique in addition to more classical approaches.
Background: Protein sequence motifs are by definition short fragments of conserved amino acids, often associated with a specific function. Accordingly protein sequence profiles derived from multiple sequence alignments provide an alternative description of functional motifs characterizing families of related sequences. Such profiles conveniently reflect functional necessities by pointing out proximity at conserved sequence positions as well as depicting distances at variable positions. Discovering significant conservation characteristics within the variable positions of profiles mirrors group-specific and, in particular, evolutionary features of the underlying sequences. Results: We describe the tool PROfile analysis based on Mutual Information (PROMI) that enables comparative analysis of user-classified protein sequences. PROMI is implemented as a web service using Perl and R as well as other publicly available packages and tools on the server-side. On the client-side platform-independence is achieved by generally applied internet delivery standards. As one possible application analysis of the zinc finger C2H2-type protein domain is introduced to illustrate the functionality of the tool. Conclusion: The web service PROMI should assist researchers to detect evolutionary correlations in protein profiles of defined biological sequences. It is available at http:// promi.mpimpgolm. mpg.de where additional documentation can be found
Spatiotemporal dynamics of the Calvin cycle multistationarity and symmetry breaking instabilities
(2011)
The possibility of controlling the Calvin cycle has paramount implications for increasing the production of biomass. Multistationarity, as a dynamical feature of systems, is the first obvious candidate whose control could find biotechnological applications. Here we set out to resolve the debate on the multistationarity of the Calvin cycle. Unlike the existing simulation-based studies, our approach is based on a sound mathematical framework, chemical reaction network theory and algebraic geometry, which results in provable results for the investigated model of the Calvin cycle in which we embed a hierarchy of realistic kinetic laws. Our theoretical findings demonstrate that there is a possibility for multistationarity resulting from two sources, homogeneous and inhomogeneous instabilities, which partially settle the debate on multistability of the Calvin cycle. In addition, our tractable analytical treatment of the bifurcation parameters can be employed in the design of validation experiments.
SLocX predicting subcellular localization of Arabidopsis proteins leveraging gene expression data
(2011)
Despite the growing volume of experimentally validated knowledge about the subcellular localization of plant proteins, a well performing in silico prediction tool is still a necessity. Existing tools, which employ information derived from protein sequence alone, offer limited accuracy and/or rely on full sequence availability. We explored whether gene expression profiling data can be harnessed to enhance prediction performance. To achieve this, we trained several support vector machines to predict the subcellular localization of Arabidopsis thaliana proteins using sequence derived information, expression behavior, or a combination of these data and compared their predictive performance through a cross-validation test. We show that gene expression carries information about the subcellular localization not available in sequence information, yielding dramatic benefits for plastid localization prediction, and some notable improvements for other compartments such as the mito-chondrion, the Golgi, and the plasma membrane. Based on these results, we constructed a novel subcellular localization prediction engine, SLocX, combining gene expression profiling data with protein sequence-based information. We then validated the results of this engine using an independent test set of annotated proteins and a transient expression of GFP fusion proteins. Here, we present the prediction framework and a website of predicted localizations for Arabidopsis. The relatively good accuracy of our prediction engine, even in cases where only partial protein sequence is available (e.g., in sequences lacking the N-terminal region), offers a promising opportunity for similar application to non-sequenced or poorly annotated plant species. Although the prediction scope of our method is currently limited by the availability of expression information on the ATH1 array, we believe that the advances in measuring gene expression technology will make our method applicable for all Arabidopsis proteins.
Describing the determinants of robustness of biological systems has become one of the central questions in systems biology. Despite the increasing research efforts, it has proven difficult to arrive at a unifying definition for this important concept. We argue that this is due to the multifaceted nature of the concept of robustness and the possibility to formally capture it at different levels of systemic formalisms (e.g, topology and dynamic behavior). Here we provide a comprehensive review of the existing definitions of robustness pertaining to metabolic networks. As kinetic approaches have been excellently reviewed elsewhere, we focus on definitions of robustness proposed within graph-theoretic and constraint-based formalisms.
Refined elasticity sampling for Monte Carlo-based identification of stabilizing network patterns
(2015)
Motivation: Structural kinetic modelling (SKM) is a framework to analyse whether a metabolic steady state remains stable under perturbation, without requiring detailed knowledge about individual rate equations. It provides a representation of the system's Jacobian matrix that depends solely on the network structure, steady state measurements, and the elasticities at the steady state. For a measured steady state, stability criteria can be derived by generating a large number of SKMs with randomly sampled elasticities and evaluating the resulting Jacobian matrices. The elasticity space can be analysed statistically in order to detect network positions that contribute significantly to the perturbation response. Here, we extend this approach by examining the kinetic feasibility of the elasticity combinations created during Monte Carlo sampling.
Results: Using a set of small example systems, we show that the majority of sampled SKMs would yield negative kinetic parameters if they were translated back into kinetic models. To overcome this problem, a simple criterion is formulated that mitigates such infeasible models. After evaluating the small example pathways, the methodology was used to study two steady states of the neuronal TCA cycle and the intrinsic mechanisms responsible for their stability or instability. The findings of the statistical elasticity analysis confirm that several elasticities are jointly coordinated to control stability and that the main source for potential instabilities are mutations in the enzyme alpha-ketoglutarate dehydrogenase.
The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44% heterosis for biomass. Mid-parent heterosis in the RILs ranged from −31 to 99% for dry weight and from −58 to 143% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.
The main objective of this study was to identify genomic regions involved in biomass heterosis using QTL, generation means, and mode-of-inheritance classification analyses. In a modified North Carolina Design III we backcrossed 429 recombinant inbred line and 140 introgression line populations to the two parental accessions, C24 and Col-0, whose F 1 hybrid exhibited 44% heterosis for biomass. Mid-parent heterosis in the RILs ranged from −31 to 99% for dry weight and from −58 to 143% for leaf area. We detected ten genomic positions involved in biomass heterosis at an early developmental stage, individually explaining between 2.4 and 15.7% of the phenotypic variation. While overdominant gene action was prevalent in heterotic QTL, our results suggest that a combination of dominance, overdominance and epistasis is involved in biomass heterosis in this Arabidopsis cross.
Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites.
Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented.
These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected.
Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.
Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites.
Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented.
These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected.
Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.